A study of erythropoiesis and iron metabolism in the rabbit in vivo. I. Characterization and limits of the physiological response.

1. An experimental model system was developed in the rabbit to study the transport of iron and the erythropoietic response to chronic bloodletting. 2. This model presents certain novel features as the capacity to measure total red blood cell production and total hemoglobin production in a daily basis. 3. Daily red blood cell production and output of hemoglobin are directly proportional to the volume of blood extracted. The limits of the erythropoietic response were determined. 4. When only minimal bloodletting was performed (3-6 ml blood/kg body weight) a normocytic response was obtained; with the removal of larger volumes of blood, a switch to macrocytic anemia was observed. Cats and guinea pigs responded in a similar fashion. 5. After induction of macrocytic anemia, the diameter of erythroid precursor cells in the bone marrow of the long bones increased and their numbers increased 11.5-fold.

Rabbit erythropoiesis during recovery from chronic anaemia induced by bleeding.

Rabbit erythropoiesis was studied during recovery from chronic anaemia induced by bleeding. Adult rabbits were made anaemic by daily removal of 10 ml of blood per Kg of body weight, through intracardiac puncture, resulting in a significant stimulation of erythropoiesis. After 14 days, bleeding was stopped and the erythropoietic response was studied during the period of recovery. Peripheral blood and bone marrow were analysed for the two weeks following the last bleeding. While levels of red blood cells and haemoglobin returned to normal values by day 6 of recovery, bone marrow erythroblasts decreased gradually until they reached the normal range by day 11. Once bleeding was stopped, there was a significant decrease in the number of circulating reticulocytes, with a concomitant increase in the number of their marrow counterpart. This suggests that release of reticulocytes from bone marrow into the circulation was temporarily blocked. There was also a rapid shift towards normocytic production and the disappearance of macrocytosis. Non-erythroid cells responded very rapidly during recovery, reaching normal values in both peripheral blood and bone marrow 3 days after the last bleeding. Our results show that under the experimental conditions described here, (i) the rabbit haemopoietic system is able to respond to dramatically different physiological stages, and (ii) since the kinetics of most parameters during the period of recovery, both in peripheral blood and bone marrow, were different from those observed during the induction of anaemia, it is possible that the mechanisms operating under both conditions are different.